Tenecteplase not superior to alteplase in mild acute ischaemic stroke
Patients with mild acute ischaemic stroke treated with tenecteplase had similar outcomes and adverse effect profile to those treated with alteplase, highlighting the nonsuperiority of tenecteplase over alteplase, results of the NOR-TEST* trial showed.
Participants in this multicentre (13 stroke units in Norway), phase III superiority trial were 1,100 individuals (median age 77 years, median NIHSS** baseline score, 4 points) with suspected acute ischaemic stroke who were eligible for intravenous thrombolysis and admitted to stroke units within 4.5 hours of symptom onset or awakening with symptoms. They were randomized to receive tenecteplase (0.4 mg/kg up to a maximum 40 mg, n=549) or alteplase (0.9 mg/kg up to a maximum 90 mg, n=551) intravenously.
With the exception of fewer patients in the tenecteplase group having a history of ischaemic heart disease, other baseline characteristics were similar between patients in both groups.
Excellent outcome, defined in this study as modified Rankin Scale [mRS] score of 0–1 at 3 months, occurred in a similar proportion of patients on tenecteplase and alteplase (64 percent vs 63 percent; odds ratio [OR], 1.08, 95 percent confidence interval, 0.84–1.38; p=0.52). [Lancet Neurol 2017;doi:10.1016/S1474-4422(17)30253-3]
Incidence of any intracranial haemorrhage within 24–48 hours of treatment was also similar between patients in the tenecteplase and alteplase groups (9 percent each; OR, 0.94; p=0.82) as was incidence of symptomatic intracranial haemorrhage (3 percent vs 2 percent; OR, 1.16; p=0.70).
“The fairly low number of patients with severe stroke might … account for the low rates of overall [and symptomatic] intracranial haemorrhage seen in both treatment groups,” said the researchers.
At 3 months, there were 29 and 26 deaths in the tenecteplase and alteplase groups, respectively (OR, 1.12; p=0.68), and frequency of serious adverse events was also comparable between groups (26 percent of patients in each group; p=0.74).
“The tenecteplase dose used in our study … was discarded by previous researchers because of safety concerns. [O]ur study showed that tenecteplase 0.4 mg/kg has a similar safety profile to alteplase 0.9 mg/kg,” the researchers said.
There were 14 readmissions to hospital among patients on tenecteplase compared with 22 among those on alteplase up to day 7, with a similar number of readmissions between groups between days 8 and 90 (63 vs 68 days).
The researchers acknowledged that the open-label design of the trial and the lack of NIHSS and mRS certification among some trial staff may have affected the results.
“Since our results might not be completely generalizable to patients with severe neurological impairment at admission, future phase III studies should investigate the safety and efficacy of tenecteplase in patients with severe stroke,” said the researchers.
“For clinical practice, probably very little will change because these results are not definitive. For clinical research, though, much more thought needs to go into the design and conduct of active comparator trials,” said Professor Craig Anderson from The George Institute for Global Health, University of New South Wales, Sydney, Australia, in a commentary. [Lancet Neurol 2017;doi:10.1016/S1474-4422(17)30277-6]
“[F]uture trials of different combinations and approaches to reperfusion therapy will need to include large enough numbers of patients to ensure reliable detection of effects in superiority or noninferiority designs, and that any benefits are supported by clear clinical care and economic gains,” said Anderson.